APPLICANT'S ABSTRACT: While the deleterious effects of excessive alcohol consumption are well recognized, the effects of moderate alcohol consumption are not well understood. Currently, it is thought that moderate alcohol consumption reduces the risk of coronary heart disease (CHD), increases bone density, is anxiolytic, and promotes social interaction. Thus, there currently appears to be some benefit to moderate alcohol consumption. More worrisome is the possibility that moderate alcohol consumption may increase breast cancer risk, and that it may also lead to excessive alcohol consumption. Hence, there may be a risk/benefit trade-off to moderate alcohol consumption. We propose to assess the effects of moderate alcohol consumption on CHD, osteoporosis, and breast cancer risk in ovariectomized female cynomolgus monkeys (Macaca fascicularis), a useful animal model for each of these endpoints. This animal model will allow randomized assignment to moderate alcohol or placebo treatment groups, thus avoiding the problems of self-selected populations and self-reported alcohol consumption inherent in human studies. The proposed experiment also offers complete control over alcohol dose, diet, and other variables known to affect disease endpoints. In the proposed experiment, hypothesized mechanisms of alcohol action will be addressed during the early and middle stages of disease development which is not possible using human subjects. Consequently, the use of this animal model obviates the need to wait for relatively rare clinical events to occur in order to obtain reliable measures of disease risk. Our long-term goal is to determine the relative risks/benefits of moderate alcohol consumption by simultaneous assessment of CHD, osteoporosis, and breast cancer risk.